Eduardo F. Marques

Abstract Polymeric hydrogels are traditionally employed as drug reservoirs in topical delivery, but they can also function as scaffolds for drug-loaded nanocarriers, enabling hybrid systems with enhanced performance. In this work, we report a thermo-adaptive hybrid hydrogel-composed of a block copolymer scaffold and a network of surfactant-based nano- and microtubes-which exhibits a mechanism herein termed inversely coupled thermogelation (ICT). The scaffold consists of Pluronic F127, a biocompatible triblock copolymer that transitions from micellar solution to a cubic liquid crystalline gel upon heating. The tubular network arises from the self-assembly of biomimetic lysine-derived surfactants. Crucially, when the block copolymer/surfactant hybrid is heated from 20 degrees C to 35 degrees C (approx. skin temperature), the surfactant tubes disassemble into micelles or vesicles, while the block copolymer forms the cubic phase. Accordingly, a tube-dominated gel evolves into a block copolymer-dominated gel through a gel-solution-gel sequence uniquely driven by the opposing thermal responses of the two constituents. This results in a hybrid system that is not only spreadable, self-healing, and mechanically robust, but also well-suited for sustained topical delivery. Imaging, calorimetry, and rheology provide detailed insights into the structure, phase transitions, and flow behavior of the hybrid system and its individual components. As a proof-of-concept, the gel enables slow, sustained release of a fluorescent model probe (carboxyfluorescein), exhibits excellent cytocompatibility, and promotes high cell internalization. Overall, this ICT-based strategy establishes a versatile and sustainable platform with strong potential for long-term topical drug delivery.

Abstract Stimuli-responsive surfactant self-assembly offers versatile opportunities to tailor colloidal structure and function through simple formulation strategies. Here, we report a photoresponsive catanionic vesicle system composed of the double-chained cationic surfactant didodecyldimethylammonium bromide (DDAB) and an anionic amphiphilic 2-hydroxychalcone derivative bearing a sulfonate headgroup (C8SCh). The self-assembly and phase behavior of the individual components and their mixtures are characterized, revealing a broad vesicle-forming compositional range. Notably, three molar fractions (xCh = 0.10, 0.20, and 0.80) yield dispersions composed exclusively of vesicles, enabling the formation of either positively or negatively charged vesicles using the same pair of molecular building blocks. Strong synergistic interactions between DDAB and C8SCh are evidenced by markedly reduced critical aggregation concentrations and negative interaction parameters. The incorporation of the chalcone photoswitch endows the vesicles with light responsiveness, inducing composition-dependent morphological rearrangements in both DDAB-rich and C8SCh-rich regimes. Under mildly acidic conditions (pH = 4.5), partial conversion of the chalcone to its flavylium form introduces an additional, independent stimulus that further modulates the structure of C8SCh-rich vesicles. This intrinsic charge tunability enables highly efficient, charge-selective electrostatic entrapment of both anionic and cationic molecular probes-carboxyfluorescein (CF) and doxorubicin (DOX), respectively-without the need for active loading strategies. Importantly, cargo release is selectively modulated by vesicle composition and external stimuli: light stimulation enhances the release of CF from DDAB-rich vesicles, while the combined action of acidification and irradiation significantly increases DOX release from C8SCh-rich vesicles. Overall, these results establish a simple catanionic system in which surface charge, morphology, and release behavior are jointly controlled by composition, light, and pH, offering a versatile and readily formulated platform with potential applications in controlled delivery.

Abstract Electrochemical energy conversion technologies are central to sustainable power generation, yet sluggish oxygen reduction reaction (ORR) kinetics remain a key limitation in alkaline fuel cells. Although Pt-based electrocatalysts are highly active, their cost and scarcity motivate the development of sustainable, carbon-based alternatives. Here, biochars derived from different parts of an abundant invasive plant, water hyacinth (WH), namely bulbs, wood and leaves, were prepared, screened, and evaluated as ORR electrocatalysts. Among them, bulb-derived biochar (WHB) showed the highest potential, and nitrogen doping produced the most pronounced enhancement. N-doped WHB exhibited an onset potential of 0.85 V, a limiting current density of-3.19 mA center dot cm-2, an electron transfer number of nO2 = 3.16 and a Tafel slope of 57 mV center dot dec-1, approaching Pt/C in activity metrics. XPS and Raman analyses linked these improvements to favorable nitrogen speciation-particularly graphitic N-and increased structural disorder. In parallel, layer-by-layer (LbL) hybridization with multi-walled carbon nanotubes (MWNTs) provided complementary insight into structure-performance relationships. Hybridization improved ORR activity when the base material was pristine WHB (among the nanocomposites, 3:1 WHB:N-MWNT performed best, with Eonset 1/4 0.81 V, jL =-3.37 mA center dot cm-2, nO2 = 3.12, and TS = 76 mV center dot dec-1), consistent with effective integration of porous biochar and conductive nanotube pathways. In contrast, adding MWNTs to already highly active N-WHB reduced performance, likely due to dilution of catalytic sites and disruption of active interfaces. Overall, this study demonstrates invasive biomass as a viable feedstock for high-performance, Pt-free ORR catalysts and highlights when chemical tuning versus hybrid assembly is most beneficial for catalyst design.

Abstract Skin cancer, particularly melanoma, remains a major therapeutic challenge due to its high metastatic potential and limited efficacy of systemic chemotherapy. Localized and controlled delivery of chemotherapeutic agents such as doxorubicin (DOX) represents a promising alternative to systemic treatments and costly immunotherapies. Hybrid hydrogels that integrate polymeric scaffolds with embedded nanostructures (e.g., vesicles, micelles, or nanoparticles) have emerged as particularly effective platforms for enhancing therapeutic performance. Herein, we report the development of a thermosensitive hybrid hydrogel for potential melanoma drug delivery applications, obtained by dispersing DOX-loaded, pH-sensitive 12-2-12/SLSar catanionic vesicles within a poloxamer 237 (F87) scaffold. The system was comprehensively characterized in terms of rheological behavior, biocompatibility, drug-release kinetics, and in vitro anti-melanoma activity in 2D monolayer cell cultures and 3D spheroids. In parallel, molecular-level interactions between the F87 matrix and the surfactant-based vesicles were investigated. Strong polymer-surfactant interactions were observed, leading to the formation of mixed polymer/surfactant micelles and vesicles, and inducing significant modifications in aggregate physicochemical properties, particularly surface charge. These interactions were found to be thermally driven and strongly dependent on the polymer-to-surfactant ratio. The catanionic vesicles exhibited high DOX encapsulation efficiency and remained stably dispersed within the F87 scaffold. The resulting hybrid hydrogel demonstrated controlled release kinetics, offering potential advantages for localized drug delivery compared with vesicle-only formulations. Moreover, the hybrid system demonstrated excellent biocompatibility and significantly outperformed neat F87 hydrogels in enhancing DOX internalization and inducing melanoma cell death in vitro. Overall, this work presents a versatile and tunable strategy for integrating catanionic vesicles into thermosensitive polymeric scaffolds, providing a promising platform for localized melanoma drug delivery.

Abstract Light-responsive control over supramolecular self-assembly provides a route to dynamically regulate nanoscale transport processes. Here we demonstrate that photoisomerization of a membrane-bound chalcone amphiphile enables light-driven reprogramming of catanionic self-assembly, producing composition-dependent morphological transitions that directly govern drug-release kinetics. Mixtures of a 2-hydroxychalcone-derived cationic amphiphile (C6NCh) with the biocompatible anionic surfactant sodium N-lauroyl sarcosinate spontaneously form stable unilamellar vesicles (hydrodynamic diameter approximate to 130-200 nm) across a broad concentration range on the anion-rich side of the phase diagram. Upon near-UV irradiation, chalcone photoisomerization and tautomerization induce marked reconfiguration of the self-assembled structures, leading either to vesicle-to-micelle transitions or to membrane reorganization with faceted vesicle morphologies, depending on composition. These light-driven structural pathways generate distinct nanoscale transport regimes, enabling bidirectional modulation of paclitaxel release kinetics. Accelerated release is observed when irradiation promotes formation of highly dynamic micellar aggregates, whereas membrane ordering and domain formation correlate with reduced permeability and slower release. Under selected conditions, zero-order release behavior is achieved, with irradiation increasing the release rate by approximately 50%. These results identify chalcone-based catanionic assemblies as a useful model system in which external stimuli reprogram self-assembly and thereby tune molecular transport, offering a conceptual basis for the design of adaptive self-assembled nanocarriers.